Diabetes mellitus is the most common cause of neuropathy in the United States, and almost 1/4 of those[unreadable] patients suffer from chronic pain. Painful diabetic neuropathy (PDN) has a significant adverse effect on[unreadable] quality of life; none of the available treatments reliably reduce the pain to a clinically significant degree.[unreadable] Herpes simplex virus (HSV) naturally targets with high efficiency to neurons of the dorsal root ganglion[unreadable] (DRG) from peripheral inoculation. In previous studies we have demonstrated that replication incompetent[unreadable] HSV-based vectors engineered to express inhibitory neurotransmitters, anti-inflammatory peptides, or the[unreadable] glial cell derived neurotrophic factor can reduce pain in rodent models of chronic pain. We propose a series[unreadable] of studies to test the hypothesis that HSV-mediated gene transfer to the DRG, achieved by subcutaneous[unreadable] inoculation of the vector, will provide a novel yet practical therapeutic strategy for the treatment of painful[unreadable] diabetic neuropathy. Five specific aims are outlined to investigate the pathogenesis of painful diabetic[unreadable] neuropathy and to explore the possibility that HSV-mediated gene transfer can be used to reduce[unreadable] mechanical hyperalgesia, mechanical allodynia, and inflammatory pain in a rodent model of diabetic[unreadable] neuropathy. These studies will also provide preclinical data towards the development of a gene therapy[unreadable] approach for PDN, a condition which is poorly controlled by available medical treatments.